DESCRIPTION (Adapted from the application): This is the first application for a Mentored Clinical Scientist Development Award from the University of California at San Francisco on behalf of Kristine Yaffe, M.D. The applicant s goal is to develop the multidisciplinary skills necessary to become a leading independent investigator in dementia research. Developmental plans include a program of course work, research seminars, and structured mentoring, as well as a research project directed toward prevention and treatment of cognitive decline and dementia in the elderly. Specifically, the applicant will investigate the role of estrogen-like drugs for prevention of preclinical cognitive decline and dementia. She has chosen studies of different methodologies (randomized trial, cross-sectional, and prospective) in order to answer several complementary questions and to further her understanding of the strengths and limitations of various study designs. This proposal has three specific aims: (1) To determine whether elderly women using postmenopausal estrogen have better baseline cognitive function and less cognitive decline over a six year period than women not taking estrogen, (2) To determine whether elderly women treated for four years with a new selective estrogen receptor modulator, raloxifene, have better cognitive function and less incidence of dementia than women treated with placebo, (3) To determine if biologic markers of estrogen status, such as bone mineral density, serum estradiol levels, and different estrogen receptor genotypes, are associated with cognitive function in elderly women. The specific aims will be achieved by analyzing data from the ongoing Study of Osteoporotic Fractures (SOF), a prospective study of nearly 10,000 elderly community-dwelling women, and from the Multicenter Osteoporosis Raloxifene Evaluation (MORE) trial of over 7,000 women who were randomized to raloxifene or placebo. Both studies include large numbers of elderly women who were not demented at baseline and who receive periodic cognitive testing during the studies. If this promising preventive intervention proves effective, millions of women could preserve their cognitive capacity and maintain their independence and quality of life. This award will foster the applicant's development towards becoming an independent investigator in aging research.